1. Field of the Invention
The present invention relates to synthetic peptides and processes for synthesizing the same, wherein the peptides are designed and synthesized based on the peptide sequence of magainins or PGS peptides. More specifically, the present invention relates to modified peptide analogues of magainins or PGS peptides and processes for designing and synthesizing the same so as to enhance antimicrobial properties exhibited thereby.
2. Description of Related Art
A variety of peptides exhibiting antimicrobial properties have been isolated from the skin of the African clawed frog Xenopus laevis. Soravia et al, "Antimicrobial properties of peptides from Xenopus granular gland secretions." Febs. Lett., 1988 Feb. 15, 228 (2), pp. 337-40. These peptides are secreted from the skin under stress and act as anti-infection agents and wound healing promoters. These peptides include a family of novel broad spectrum antimicrobial peptides known as magainins, also known as PGS peptides. Zasloff, "Magainins, a class of antimicrobial peptides from Xenopus skin: isolation, characterization of two active forms, and partial cDNA sequence of a precursor," Proc. Natl. Acad. Sci. USA, 1987 Aug., 84 (15), pp. 5449-53; Terry et al, "The cDNA sequence coding for prepro-PGS (prepro-magainins) and aspects of the processing of this prepro-polypeptide," J. Biol. Chem., 1988 Apr. 25, 263 (12), pp. 5745-51. Magainins include two closely related peptides that each contain 23 amino acids and differ by two substitutions. These peptides are water soluble, nonhemolytic at their effective antimicrobial concentrations, and exhibit an alpha-helical structure with amphiphilic character. Marion et al, "A two-dimensional NMR study of the antimicrobial peptide magainin 2," Febs Lett., 1988 Jan. 18, 227 (1), pp. 21-6. At low concentrations they inhibit the growth of numerous species of bacteria and fungi and induce osmotic lysis of protozoa. The sequence of a partial cDNA of the precursor reveals that the peptides derive from a common larger protein. These peptides appear to represent a previously unrecognized class of vertebrate antimicrobial activities.
Two magainins which have been isolated, i.e. magainin 1 and magainin 2, have been synthetically prepared and it has been demonstrated that the synthetic magainin peptides appear to be indistinguishable from the natural products with respect to chromatographic properties and biological activity. Zasloff et al, "Antimicrobial activity of synthetic magainin peptides and several analogues," Proc. Natl. Acad. Sci. USA. 1988 Feb., 85 (3), pp. 910-3. Although the antimicrobial properties exhibited by magainins are useful, it is desirable to improve these properties. The presence of amphiphilic structures in peptides, such as magainins, often leads to an ability to disrupt cell or organelle membranes or to form a channel affecting ion flux. These natural peptides, however, contain amino acid residues in the middle of the peptide chain having a low propensity for alpha-helical formation with amphiphilic structural characteristics. These peptides also appear to be susceptible to serum protease cleavage. Thus, the structural characteristics of magainins apparently reduce their potential for antimicrobial activity.